The study assessed the eye movements of 60 adult German readers during silent reading of target words, consisting of two and three syllables, embedded in sentences. The first objective was to assess whether the inhibitory effect of first syllable frequency, which was up to now primarily shown for isolated words, generalises to natural reading. The second objective was to assess the effect of orthographic similarity. First syllable frequency was defined phonologically and was based on the SUBTLEX norms for spoken language [Brysbaert et al. (2011). The word frequency effect: A review of recent developments and implications for the choice of frequency estimates in German. "Experimental Psychology," 58, 412-424]. Orthographic similarity was indexed by orthographic Levenshtein distance neighbourhood frequency (NF) [Yarkoni, T., Balota, D. & Yap, M. (2008). Moving beyond Coltheart's N: A new measure of orthographic similarity. "Psychonomic Bulletin & Review," 15, 971-979]. We found inhibitory effects for first syllable frequency and for orthographic NF. First syllable frequency affected first fixation duration which was considered as reflecting early effects in visual word recognition. Orthographic NF affected "late" measures. These findings show that, first, the effect of first syllable frequency does generalise to silent reading. Second, the effect of orthographic NF, up to now investigated only for short words in the context of English, does generalise to multisyllabic words in the German orthography. Relating the effects to the individual reading rate of the participants revealed that the effects were consistent in fast readers but highly variable in slow readers.